Method and apparatus for measurement of an ultrafiltration rate in a renal replacement therapy device

ABSTRACT

A system of identifying an ultrafiltration rate in a renal replacement therapy device is provided, wherein the system includes a controller connected to a first flow sensor obtaining flow rate data from a blood withdrawal line and a second sensor obtaining flow rate data from a blood delivery line. The controller calibrates, such as matches, the first flow sensor and the second flow sensor from flow measurements during periods of known ultrafiltration by the renal replacement therapy device. The controller is further configured to perform periodic equalization of the flow sensors, at a known ultrafiltration rate during the treatment session. The controller can employ flow rate data from the calibrated or equalized first flow sensor and the second flow sensor to calculate an ultrafiltration rate of the renal replacement therapy device based on the measured blood flow into and out of the renal replacement therapy device. The calibration can be performed before, during, or after blood treatment in a treatment session.

CROSS-REFERENCE TO RELATED APPLICATIONS

Not applicable.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

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THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT

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REFERENCE TO A SEQUENCE LISTING

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STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINTINVENTOR

Not applicable.

BACKGROUND OF THE INVENTION Field of the Invention

The present disclosure relates to an apparatus and method foridentifying, with improved accuracy, an ultrafiltration rate of a renalreplacement therapy device based on a measured blood flow in a bloodwithdrawal line to the renal replacement therapy device and a measuredblood flow in a blood delivery line from the renal replacement therapydevice.

Description of Related Art

A variety of different medical treatments relate to the delivery offluid to, through and/or from a patient, such as the delivery of bloodbetween a patient and an extracorporeal system. For example,hemodialysis, hemofiltration, and hemodiafiltration are all renalreplacement therapies that remove waste, toxins, and excess water fromthe blood, wherein during these treatments, the patient is connected toan extracorporeal system having a treatment or renal replacement device,and the blood is pumped through the system and the device, wherein thewaste, toxins, and fluid are removed from the blood, and the cleanedblood is returned to the patient.

In dialysis therapy, blood is extracted from the body and conveyedthrough the extracorporeal system to a dialyzer. Blood flows into thedialyzer via a blood inflow port, flows through hollow fiber membranesand out from an outflow port, and is returned to the patient.Simultaneously, dialysate is supplied into the casing via a dialysateinflow/outflow port to fill between the hollow fiber membranes. Theblood and dialysate undergo substance exchange via the hollow fibermembranes.

In order to substitute for the function of the kidney in adjusting thewater content, the dialyzer is used to perform fluid removal fordischarging excessive water content out of the body during the dialysistherapy. In the fluid removal process, the flow of dialysate iscontrolled to increase the quantity of outflow of dialysate compared tothe quantity of inflow of dialysate, so that negative pressure isgenerated within the casing thereby extracting the water content withinthe blood across the semi-permeable membrane toward the dialysate (i.e.,by ultrafiltration).

The withdrawal of fluid in the dialyzer, also known as ultrafiltration,is given by the difference between the spent dialysate pumped out of thedialyzer and the fresh dialysate pumped into the dialyzer. Because ofthe large volume of dialysate that is exposed to the membrane in thedialyzer during dialysis therapy, there is a need for accurate controlof the ultrafiltration. In hemodialysis for example, typically about 200liters of dialysate are passed through the dialyzer during a treatmentsession. The target amount of ultrafiltrate during a treatment sessionis typically about 2 to 3 liters and may need to be controlled with amaximum deviation of the order of only 0.1 to 0.2 liter. Accordingly, inthis example, ultrafiltration may need to be controlled with a maximumerror of approximately 1:1000 in relation to the total flow ofdialysate.

Currently, the standard of accurate ultrafiltration measurementsrequires expensive equipment to be deployed in hemodialysis machines.For example, current systems include two scale set before and after thedialyzer on dialysate side. However, these systems are relativelycomplicated and can impart operator error.

BRIEF SUMMARY OF THE INVENTION

The present disclosure addresses a current issue in blood flowmeasurement systems with flow sensors for measuring ultrafiltration,where the errors in measurement from the flow sensors are much greaterthan the necessary accuracy of measurements for determining fluidremoval by a renal replacement therapy device.

For example, a current specification of an error “d” in blood flowmeasurement in hemodialysis lines by manufacturers of ultrasound transittime sensors is d = ± 6%. This error is caused by multiple factorsincluding: error in factory calibration of the equipment, nonlinearityof the flow vs. recorded voltage, the influence of blood temperature andambient temperature on the functioning of the sensors and theirelectronic performance, deviation of the tubing in the system from afactory calibration, deviations within the tubing used in the field, aswell as variations in the density of the blood, including hematocrit andion concentration. These flow measurement errors can manifest as: (i)deviation of the slope (angle) of a curve or graph of recorded flow vspump flow setting (or actual flow), and (ii) fluctuation of theY-intercept (FIGS. 3A and 3B).

This means that for an error d = ± 6%, in an exemplary blood flow of 300ml/min, the error will be within ± 18 ml/min. Considering thatultrafiltration is the difference between Q_(A)-Q_(V), then the error,if independent from variables, will be [(da)2+(dv)2]½ ≈ ± 8.5% or ≈ ± 25ml/min at 300 ml/min flow rate in the renal replacement therapy device.Considering for example, the removal of fluid from a patient through anultrafiltration rate (UF) is typically on the order of 600 ml/hour whichis 10 ml/min. Therefore, if one wants to measure UF with the errorwithin 10% of the flow rate, this requires UF needs to be measured witherror ± 1 ml/min (for UF = 10 ml/min). Thus, an error of error ± 1ml/min for a 300 ml/min blood flow through the renal replacement therapydevice requires a measurement within ± 0.3 % error. The available errorof UF measured by current flow sensors is approximately ± 25 ml/minwhich is almost 30 times larger than the error that is needed forproviding useful UF measurements.

Generally, the present method and apparatus encompass measuring, withcalibrated flow sensors, blood flow of an input line and an output lineof the renal replacement therapy device, and based on a differencebetween blood flow into the renal replacement therapy device (blood flowof the input line) and blood flow out of the renal replacement therapydevice (blood flow out of the output line), and assessing fluild removal(ultrafiltration) during a blood treatment session, wherein theultrafiltration can be measured substantially continuously during thetreatment session.

The present disclosure contemplates calibrating a first flow sensormeasuring blood flow of the input line and a second flow sensormeasuring blood flow out of the output line, wherein the difference inmeasured flow is used to determine ultrafiltration. It is understoodcalibrated flow sensors includes the first flow sensor being calibrated,or the second flow sensor being calibrated, or both the first flowsensor and the second flow sensor being calibrated.

In general, the disclosure contemplates a calibration of the flowsensors, wherein the calibration can be a flow sensor matching or a flowsensor equalization. In the flow sensor matching, the flow sensors areexposed to a plurality of different common flow rates through theextracorporeal circuit, with a known, such as zero ultrafiltration,wherein the flow sensors are standardized to provide the same measure ofthe same flow. That is, the matching provides that measurement signalsfrom the flow sensors as disposed within an extracorporeal circuit willprovide equal readings of a common flow. In the flow sensorequalization, the matched flow sensors are subsequently exposed to acommon flow, with a known ultrafiltration rate, such as a zeroultrafiltration rate, and the flow sensors are equalized to provide thesame measure for the common flow, by either adjusting the first flowsensor, the second flow sensor or both flow sensors so as to provide anequal measure of the common flow. That is, the equalization providesthat the signals from one flow sensor are equalized to the signals fromthe second flow sensor. It is contemplated that equalization can beperformed periodically during a treatment session.

The present disclosure provides an apparatus for measuringultrafiltration and particularly an ultrafiltration rate of a renalreplacement therapy device in an extracorporeal circuit, wherein therenal replacement therapy device includes or is operably coupled to ablood input line delivering blood to the renal replacement therapydevice, a pump, a permeable membrane, a blood output line passing bloodfrom the renal replacement therapy device, and is configured toestablish a known, such as zero ultrafiltration rate and a targetultrafiltration rate, the apparatus including a first flow sensorconfigured to measure a blood input line flow in the blood input line; asecond flow sensor configured to measure a blood output line flow in theblood output line; and a controller connected to the first flow sensorand the second flow sensor, wherein the controller is configured tocalibrate, based on blood flow in the extracorporeal circuit, the firstflow sensor and the second flow sensor. It is contemplated thecontroller is further configured to determine an ultrafiltration rateand ultrafiltration volume of the renal replacement therapy device.

It is understood the calibration of the first flow sensor and the secondflow sensor can include matching the flow sensors such that the flowsensors indicate an equal measure of flow at a given pump flow rate anda known, such as zero ultrafiltration, and particularly with thespecific tubing and environmental conditions of the extracorporealcircuit and the treatment session. That is, the calibration is not abench or factory calibration, but rather can be a matching of the flowsensors for accommodating the particular equipment of the givenextracorporeal circuit and treatment session, wherein the first flowsensor and the second flow sensor are matched to each other based onblood flow through the extracorporeal circuit. The matching encompassesan adjustment of the flow sensor or the obtained measurements whichaccount for external factors or to allow comparison with the measurementdata from another flow sensor in the system. As set forth below, thematching can include adjusting the measurements of one or both of thenow sensors, employing a compensating or adjusting factor to themeasurements, or signals, of one or both of the flow sensors, as well asa lookup table, or a mechanical adjustment of the respective flowsensor. Thus, it can be described that the matched first flow sensor andthe second flow sensor are calibrated.

The calibration can also include equalizing the first flow sensor andthe second flow sensor or removing any offset of the signals at a commonflow rate at a known or zero ultrafiltration. That is, it is understoodthe calibration does not require the signals generated by the respectiveflow sensor be equal, but rather the signal from one flow sensor isequalized to the signal from the remaining flow sensor.

Calibrating the first flow sensor to the second flow sensor meanscalibrating the sensors such that the signal from each sensor at acommon flow rate and a known or zero ultrafiltration are taken ortreated as indicating the same flow rate. Matching the first flow sensorto the second flow sensor for at least two common flow rates at a knownor zero ultrafiltration in the extracorporeal circuit provides a twopoint calibration. Equalizing the first flow sensor and the second flowsensor at a single common flow rate and a known or zero ultrafiltrationare taken or treated as indicating the same flow rate provides a singlepoint calibration. That is, the present disclosure contemplates onepoint calibration, as well as two point calibration to re-scale theoutput of the respective flow sensor. Two point calibration can be usedin cases where the sensor output is known to be sufficiently linear overthe measurement range and is capable of correcting both slope and offseterrors.

It is understood that zero ultrafiltration rate means no liquid ispassing through the permeable membrane in the renal replacement therapydevice. The zero ultrafiltration rate can be obtained by, but is notlimited to, stopping ultrafiltration or bypassing the renal replacementtherapy device to provide an absolute zero ultrafiltration rate, It isfurther contemplated that a known ultrafiltration rate instead of a zeroultrafiltration rate or in combination with zero ultrafiltration ratecan be implemented to be used in the present system for the calibrationprocess. For purposes of description, the term known ultrafiltrationrate will be used, wherein a zero ultrafiltration rate is an exemplaryknown ultrafiltration rate.

The present method and apparatus can improve the accuracy in measuringultrafiltration in the renal replacement treatment session by thefollowing steps: (i) before starting ultrafiltration in the treatmentsession, calibrating, such as matching, a first flow sensor and a secondflow sensor against each other for at least two flow rates, or through agiven flow range; (ii) during the treatment session, periodicallycalibrating, such as equalizing, the first flow sensor and the secondflow sensor against each other at a known ultrafiltration rate to removeany offset between the flow sensors occurring or generated during therenal replacement treatment session; (iii) averaging flow measurementsof the first flow sensor and the second flow sensor over a sufficientperiod of time to reduce, or substantially eliminate, flow measurementerror caused by pulsations in the measured flow; (iv) assessing a targetultrafiltration rate based on measurements from the calibrated firstflow sensor and the second flow sensor (such as a difference betweenadjusted flow measurements from the first flow sensor and the secondflow sensor), and (v) estimating an amount of fluid removal in the renalreplacement treatment session. It is contemplated that calibrating thefirst flow sensor and the second flow sensor includes matching thesensors, which can remove potential sensor factory calibrationinaccuracy.

The present disclosure provides a method of matching a first flow sensorand a second flow sensor to compensate for the real-time conditions suchas tubing material, temperature, etc. of the treatment session and canbe done before, during or after treatment of the blood in the treatmentsession. The matching includes the steps of (i) registering, at a knownor zero ultrafiltration rate, a flow measured by the first flow sensorand the second flow sensor, at a minimum of two pump flow rates (withinan expected flow range during the treatment session); (ii) identifying aslope of a curve of measured flow for the first flow sensor and thesecond flow sensor; (iii) identifying a correction factor to match aslope of the first flow sensor and the second flow sensor; and (iv)applying the correction factor to a flow measured during ultrafiltrationin the treatment session by at least one of the first flow sensor andthe second flow sensor. It is understood that matching can be donebefore, during or after flow measurement from the flow sensors during atreatment session, wherein the measurements are subsequently adjusted toaccommodate the matching of the flow sensors.

Matching the flow sensors can be performed at any time during thetreatment session; however, it is advantageous to identify thecalibration or correction factor prior to the treatment session. In caseof calibrating the flow sensors during or at the end of the treatmentsession, the ultrafiltration rate or amount of fluid removed is(re)calculated upon application of the sensor calibration.

The present disclosure also provides a method of calibrating the flowsensors, such as equalizing the first flow sensor and the second flowsensor during the treatment session to remove potential offset betweenthe sensors, that may occur during the treatment session. The methodincludes the steps of (i) turning off ultrafiltration (operating at aknown or zero ultrafiltration rate) for a short period of time (e.gbetween 1 second and 360 seconds, or between 10 seconds and 90 seconds,or on the order 30 seconds +/- 15 seconds); (ii) identifying an offsetbetween the first and the second flow sensor by calculating differencebetween the respective flow measured by the sensors; and (iii)calibrating, by equalizing, subsequent flow measurements of the firstand second flow sensors by the identified offset.

It is recognized that the blood flow signals registered by the first andthe second flow sensors are highly pulsatile which can produce errors inan instantaneous flow measurement (FIG. 5 ). The present method andapparatus provide a method to reduce error in flow measurement due topulsatile flow signal. The method contemplates a sufficient period ofdata collection for the flow measurement to include at least one fullcycle of pulsatile flow signal within the averaging to reduce, oreliminate, flow measurement error from the fluctuation in pulsations.Measuring the flow over a sufficient time reduces the error from thepresence the pulsations in the flow and averaging over a period reducesthe error from fluctuations in the pulsations. It is furthercontemplated the flow measurements can be taken at a common point withinthe pulsatile cycle.

In one configuration, the present disclosure provides an apparatus formeasuring an ultrafiltration rate of a renal replacement therapy devicein an extracorporeal circuit having a pump, the renal replacementtherapy device configured to establish a first and a second knownultrafiltration rate, which can be a zero ultrafiltration rate, and atarget ultrafiltration rate, the renal replacement therapy device havinga blood input line delivering blood to the renal replacement therapydevice, a permeable membrane, a blood output line passing blood from therenal replacement therapy device, the apparatus including a first flowsensor configured to measure a flow rate in the blood input line; asecond flow sensor configured to measure a flow rate in the blood outputline; and a controller connected to the first flow sensor and the secondflow sensor, the controller configured to (i) register a first flow ratemeasured by the first flow sensor and a first flow rate measured by thesecond flow sensor each at a first pump rate and the first knownultrafiltration rate, (ii) register a second flow rate measured by thefirst flow sensor and a second flow rate measured by the second flowsensor each at a second pump rate and the second known ultrafiltrationrate, (iii) calibrate at least one of the first flow sensor and thesecond flow sensor corresponding to the first flow rate measured by thefirst flow sensor, the first flow rate measured by the second flowsensor, the second flow rate measured by the first flow sensor, and thesecond flow rate measured by the second flow sensor, and (iv) identifythe target ultrafiltration rate from a third flow rate measured by thefirst flow sensor and a third flow rate measured by the second flowsensor during the target ultrafiltration rate,

A method is provided of measuring a target ultrafiltration rate by arenal replacement therapy device in an extracorporeal circuit having apump, the renal replacement therapy device configured to provide a firstknown ultrafiltration rate, a second known ultrafiltration rate, and thetarget ultrafiltration rate, and having a blood input line deliveringblood to the renal replacement therapy device, a permeable membrane, anda blood output line passing blood from the renal replacement therapydevice, the method including measuring, at a first pump flow rate andthe first known ultrafiltration rate, (i) a first flow rate in the bloodinput line by a first flow sensor and (ii) a first flow rate in theblood output line by a second flow sensor; measuring, at a second pumpflow rate and the second known ultrafiltration rate, (i) a second flowrate in the blood input line by the first flow sensor and (ii) a secondflow rate in the blood output line by the second flow sensor;calibrating at least one of the first flow sensor and the second flowsensor corresponding to the first flow rate in the blood input linemeasured by the first flow sensor, the first flow rate in the bloodoutput line measured by the second flow sensor, the second flow rate inthe blood input line measured by the first flow sensor, and the secondflow rate in the blood output line measured by the second flow sensor;measuring, during the target ultrafiltration rate and a target pump flowrate, (i) a third blood flow rate in the blood input line by thecalibrated first flow sensor and (ii) a third blood flow rate in theblood output line flow by the calibrated first flow sensor; andidentifying, at the target ultrafiltration rate and the target pump flowrate, the target ultrafiltration rate corresponding to the third bloodflow rate in the blood input line measured by the calibrated first flowsensor and the third blood flow rate in the blood output line flowmeasured by the calibrated second flow sensor.

A further method is provided in the present disclosure of measuring atarget ultrafiltration rate by a renal replacement therapy device in anextracorporeal circuit having a pump, the renal replacement therapydevice configured to provide a first known, such as zero,ultrafiltration rate, a second known, such as zero, ultrafiltrationrate, and the target ultrafiltration rate, and having a blood input linedelivering blood to the renal replacement therapy device, a permeablemembrane, and a blood output line passing blood from the renalreplacement therapy device, the method including calibrating a firstflow sensor configured to sense a flow rate in the blood input line anda second flow sensor configured to sense a flow rate in the blood outputline, wherein the calibrating corresponds to at least (i) a first flowrate in the extracorporeal circuit measured by each of the first flowsensor and the second flow sensor at a first pump flow rate and thefirst known ultrafiltration rate, and (ii) a second flow rate in theextracorporeal circuit measured by each of the first flow sensor and thesecond flow sensor at a second pump flow rate and the second knownultrafiltration rate; and identifying the target ultrafiltration ratecorresponding to a third flow rate measured by the calibrated first flowsensor and the second flow sensor at a given pump flow rate and thetarget ultrafiltration rate.

The following will describe embodiments of the present disclosure, butit should be appreciated that the present disclosure is not limited tothe described embodiments and various modifications of the invention arepossible without departing from the basic principles. The scope of thepresent disclosure is therefore to be determined solely by the appendedclaims.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

FIG. 1 is a schematic of a representative extracorporeal circuitincluding a renal replacement therapy device.

FIG. 2 is a graph of a flow profile through the extracorporeal circuitduring a treatment session showing calibration including flow sensormatching and flow sensor equalization,

FIG. 3A and FIG. 3B are comparison graphs of a flow sensor matchingprocedure, where the curves on the graph of FIG. 3A show the flowmeasurement of the first flow sensor and the second flow (venous) sensorfor multiple pump flow rate settings at a zero ultrafiltration rate. Thecurves in the graph of FIG. 3B show the flow rate data from the secondflow (venous) sensor is calibrated, such as by adjusting the flow ratedata from the first flow (arterial) sensor.

FIG. 4A and FIG. 4B are graphs showing a flow sensor equalizingprocedure, wherein in every d period, the ultrafiltration UF of therenal replacement therapy device is turned off (UF = 0) for calibrating,such as matching, equalizing or adjusting the first (arterial) flowsensor arterial and the second (venous) sensor against each other. Thegraph in FIG. 4A shows the flow measurement before calibrating, such asequalizing the flow sensors periodically, and the graph in FIG. 4B showsflow measurement after applying periodic calibration.

FIGS. 5A - 5G are a series of graphs showing the impact of the durationof flow measurements that are averaged to obtain a flow measurement(shown in a shaded panel in each graph). From FIG. 5A to FIG. 5G, thetime period (shown as shaded) is increased to include more cycles in theaveraging. FIGS. 5A - 5G show the effect of the averaging time period onreducing the impact of the pulsatile component on the measured flow.

FIG. 6 is a representative flow chart of calibrating the flow sensors bymatching the flow sensors in the extracorporeal circuit.

FIG. 7 is a representative flow chart of calibrating the flow sensors byequalizing the flow sensors in the extracorporeal circuit.

FIGS. 8A and 8B are representative flow charts of calibrating the flowsensors by matching and equalizing the flow sensors in theextracorporeal circuit.

DETAILED DESCRIPTION OF THE INVENTION

Generally, the present disclosure is directed to a renal replacementtherapy device 130. In one configuration, the present disclosure isdirected to an extracorporeal renal replacement therapy device 130,capable of generating a pressure differential across a semi-permeablemembrane to provide ultrafiltration and hence an ultrafiltration rate.

Renal replacement therapy is directed to two primary objectives, thefirst objective is to remove kidney failure-related toxins and thesecond objective is to remove excess water and salt from the blood.Generally, renal replacement therapy employs two physiologies for soluteand fluid movement. Both methods require sequestration of blood on oneside of a semi-permeable membrane.

These treatments may be performed by pumping a dialysis fluid through atreatment device such as the renal replacement therapy device 130,commonly referred to as a dialyzer, in which fluid and substances aretransported over a semi-permeable membrane. Diffusive mass transportthrough the membrane is predominant in hemodialysis (HD), whereashemofiltration (HF) uses mainly convective mass transport through thesemi-permeable membrane; and hemodiafiltration (HDF) is a combination ofthe two methods.

In diffusive clearance (dialysis), solute moves down its concentrationgradient, from areas of higher concentration to areas of lowerconcentration, The solute must be of appropriate size and charge to passthrough a semi-permeable membrane. By passing fluid across the membranecountercurrent to blood flow, equilibration of plasma and dialysatesolute concentrations occur. This process may remove or add solute tothe plasma water space depending upon the relative concentrations indialysate and plasma. Water will also move along a gradient, in thiscase the osmolar or osmotic gradient, in effect “following” the solute.Diffusive clearance is more effective at removal of small solute, suchas serum ions and urea, than for larger solute.

Convective clearance (hemofiltration or ultrafiltration) utilizes apressure gradient rather than concentration gradient and has its maineffect on water movement with solute movement in conjunction with water.The transmembrane pressure difference is increased as needed to “push”water through the membrane down a pressure gradient. This bulk flow ofplasma water “drags” solute with it (convective mass transfer) in theformation of ultrafiltrate. Small solute removal is nearly the same aswith diffusion, but fluid removal is far superior with convectiveclearance. Additionally, clearance of small solute is equivalent todiffusion, but convection demonstrates increased middle molecule(500-5,000 Dalton) clearance and is limited by membrane characteristics.Thus, ultrafiltration includes the generation of a pressure gradientacross the permeable membrane of the dialyzer to impart fluid flow fromthe blood to the dialysate.

During hemodialysis, water and sodium are not ordinarily removed bydiffusion but rather through the process of ultrafiltration.Ultrafiltration is commonly accomplished by lowering the hydrostaticpressure of the dialysate compartment of the dialyzer, thus allowingwater containing electrolytes and other permeable substances to movefrom the plasma to the dialysate. For purposes of the description, theterm ultrafiltration is taken to encompass the withdrawal of fluid inthe dialyzer including both ultrafiltration and hemofiltration.

The present disclosure provides for improving the accuracy inmeasurement of the withdrawal of fluid in the dialyzer, through themeasurement of blood flow into the dialyzer and blood flow out of thedialyzer. Specifically, the present system provides for calibrating,such as but not limited to matching and equalizing, blood flowmeasurements by a first flow sensor measuring blood flow into thedialyzer and a second flow sensor measuring blood flow out of thedialyzer so as to provide a blood side measurement system foridentifying and quantifying a rate of liquid transfer into or out of theblood side of the renal replacement therapy device.

For purposes of description, it is understood the term “blood” includestreated or untreated blood, including artificial or natural blood, aswell as plasma. As used herein, it is understood the term “identify”means to establish or indicate what something is, and encompasses theterm “quantify,” wherein the term “quantify” means to express or measurethe quantity. The ultrafiltration, which is the removal of fluid fromthe blood, can be measured, wherein the ultrafiltration is set forth asa rate (volume per unit time) and thus volume can be calculated bymultiplying the time at the measured ultrafiltration rate.

Referring to FIG. 1 , an extracorporeal circuit 100 is shown connectedthrough an access device 200 to a circulatory system of a patient. Inone configuration, the extracorporeal circuit 100 provides for renalreplacement therapy, wherein the extracorporeal circuit includes therenal replacement therapy device 130 having a permeable membrane 132.The renal replacement therapy includes, but is not limited tohemodialysis, hemofiltration, and hemodiafiltration.

The access device 200 fluidly connects to a circulatory system such as ahuman (or animal) circulatory system which includes blood, a vascularsystem having a cardiopulmonary system and a systemic system connectingthe cardiopulmonary system to the tissues of the body, and a heart.Specifically, the systemic system passes the blood though the vascularsystem (arteries, veins, and capillaries) throughout a patient body.Thus, the access device 200 fluidly connects to the circulatory systemand provides access to the extracorporeal circuit 100. The term “accessdevice” encompasses any access to the circulatory system of the patientand includes but not limited to catheters, needles, shunts, AV nativefistulae, AV-artificial graft; as well as a venous catheter, or othervascular implantations. The connection of the extracorporeal circuit 100to the patient, via the access device 200, usually includes catheters orcannulas or needles, e.g. dialysis cannulas, where the access device200, for example, is punctured and fluid communication is established.Thus, the access device 200 can include a patient blood withdrawal site110 and a patient blood delivery site 160. As set forth herein, theaccess device 200 encompasses the patient blood withdrawal site 110 aswell as the patient blood delivery site 160. Thus, the access device 200includes separate arterial access and venous access as well as arterialaccess and venous access that are proximal or adjacent, or within acommon shunt line, or graft.

The extracorporeal circuit 100 extends from the patient blood withdrawalsite 110 through the renal replacement therapy device 130 and back tothe patient blood delivery site 160, and includes a pump 170 configuredto pump blood through the extracorporeal circuit 100 from the bloodwithdrawal site, through the renal replacement therapy device and to thepatient blood delivery site.

The renal replacement therapy device 130 includes a blood input line 120delivering blood from the withdrawal site 110 to the renal replacementtherapy device, a permeable membrane and a blood delivery line 150delivering blood from the renal replacement therapy device to thepatient blood delivery site 160. A blood delivery line 150 connects theflow of the extracorporeal circuit 100 to the circulatory system, suchas through the access device 200. The blood delivery line 150 typicallyincludes a return cannula providing the fluid connection to the accessdevice 200. Although the pump 170 is shown located in the extracorporealcircuit 100, it is understood the pump can be incorporated into therenal replacement therapy device 130. Similarly, the blood input line120 and the blood delivery line 150 can be part of the extracorporealcircuit 100 or the renal replacement therapy device 130 withoutdeviating from the scope of the present disclosure. As well known in theart, the renal replacement therapy device 130 is configured to provide aknown ultrafiltration rate, such as a zero ultrafiltration rate and atleast one, and in certain configurations, a plurality of targetultrafiltration rates. The zero ultrafiltration rate means that noliquid passing through the membrane 132 from the blood side to thedialysate side. Similarly, the pump 170 is configured to provide aplurality of flow rates in the extracorporeal circuit 100 and hencethrough the renal replacement therapy device 130.

The pump 170 can be any of a variety of pumps types, including but notlimited to a peristaltic, a roller, an impeller, or a centrifugal pump.The pump 170 induces a blood flow rate through the extracorporealcircuit 100. Depending on the specific configuration, the pump 170 canbe directly controlled at the pump or can be controlled through acontroller 180 to establish a given blood flow rate in theextracorporeal circuit 100. The pump 170 can be at any of a variety oflocations in the extracorporeal circuit 100, and is not limited to theposition shown in FIG. 1 . In one configuration, the pump 170 is acommercially available pump and can be set or adjusted to provide any ofa variety of flow rates, wherein the pump flow rate can be read by auser and/or transmitted to and read by the controller 180. In oneconfiguration, the pump 170 can provide a plurality of flow rates withina given range.

Depending upon the configuration of the extracorporeal circuit 100 andthe mechanisms for measuring the blood parameters, the blood withdrawalline 120 can also include or provide an introduction port as a site forintroducing a material into the extracorporeal circuit 100. Although notshown, it is contemplated the extracorporeal circuit 100 andspecifically the blood delivery line 150 can include an air trap and airdetector between the renal replacement therapy device 130 and the accessdevice 200.

As the extracorporeal circuit 100 is configured to provide dialysis, theblood withdrawal line 120 may sometimes be referred to as an arterialline and the blood delivery line 150 may sometimes be referred to as avenous line. The “arterial line” or side is that part of theextracorporeal circuit 100 which blood passes from the patient bloodwithdrawal site 110, such as the access device 200 to flow to the renalreplacement therapy device 130. The “venous line” or side is that partof the extracorporeal circuit 100 which blood passes from the renalreplacement therapy device 130 to the patient blood delivery site 160,such as the access device 200. For purposes of description in terms ofdialysis nomenclature, the blood travels from the patient bloodwithdrawal site 110 (in the access device 200) to the arterial line 120(the blood withdrawal line) and returns to the patient blood deliverysite 160 (in the access device) through the venous line 150 (the blooddelivery line).

In the present disclosure, the term “upstream” of a given positionrefers to a direction against the flow of blood, and the term“downstream” of a given position is the direction of blood flow awayfrom the given position.

A first flow sensor 126 is configured to measure flow rate in the bloodwithdrawal line 120 by obtaining blood flow rate data from the bloodwithdrawal line and a second flow sensor 156 is configured to measureflow rate in the blood delivery 150 by obtain blood flow rate data fromthe blood delivery line. In the dialysis nomenclature, the first flowsensor 126 obtaining flow rate data in the blood withdrawal (arterial)line 120 may sometimes be referred to as the arterial flow sensor andthe second flow sensor 156 obtaining flow rate data in the blooddelivery (venous) line 150 is referred to as the venous flow sensor.

The term “flow sensor” encompasses any sensing device that provides asignal representing the flow rate data or data from which the flow rate,any pulsation, variation, frequency change, or oscillation in the flowrate, or surrogate of the flow rate, pulsation, variation, frequencychange, or oscillation in the flow rate can be determined, or sensed.

The normal or forward blood flow through the extracorporeal circuit 100includes withdrawing blood through the arterial line 120 from the accessdevice 200, passing the withdrawn blood through the extracorporealcircuit (to treat the blood in the dialyzer 130), and introducing thewithdrawn (or treated) blood through the venous line 150 into the accessdevice. The pump 170 can induce a blood flow through the extracorporealcircuit 100 from the access device 200 and back to the access device.

The first flow sensor 126 and the second flow sensor 156 are operativelycoupled to the respective line and are configured to obtain flow ratedata, where the term “flow rate data” is any data from which a flow ratecan be derived, assessed, or calculated, as well as any surrogate datafor deriving, assessing, or calculating the flow rate. It is furthercontemplated that the flow rate can be the actual blood flow rate, thecalculated blood flow rate, or a predicted flow rate, as well as anysurrogate of the actual blood flow rate, such as but not limited to aflow velocity, or a value proportional or related to the blood flow orthe velocity. The flow rate data encompasses any signals or data relatedto the blood flow, and particularly related to any pulsatile, varying,frequency dependent, or oscillatory component or characteristic orvariation of the flow, such as indicated by any signals, such as but notlimited to optical signals, acoustic signals, electromagnetic signals,temperature signals and other signal that can be source of frequencyanalysis. Thus, the flow rate data includes any signals or datarepresenting the flow rate or signals or data from which the flow rate,or any pulsation, variation, frequency variation, or oscillation of theflow rate, or pulsation, variation, frequency variation, or oscillationin the flow rate can be determined, or sensed, or any correspondingsurrogates. For example, markers in the blood, including native orintroduced particles could be used as the surrogate. Thus, the term flowrate is intended to encompass any value or measurement that correspondsto, is a surrogate of, or can represent the blood flow and especially toany pulsation, variation, frequency variation, oscillation, or acharacteristic or property of the blood flow. The term “flow rate” (or“blood flow rate”) thus encompasses the volumetric flow rate as ameasure of a volume of liquid passing a cross-sectional area of aconduit per unit time, and may be expressed in units of volume per unittime, typically milliliters per min (ml/min) or liters per minute(l/min), and any of its surrogates. It is understood the blood flow ratecan be measured as well as calculated by any of a variety of knownsystems and methods. For purposes of description, measuring the flowrate encompasses obtaining or measuring the flow rate data.

Thus, the first flow sensor 126 and the second flow sensor 156 caninclude a flow rate sensor, an ultrasound sensor or even a dilutionsensor for sensing passage of the indicator through the extracorporealcircuit 100. The first flow sensor 126 and the second flow sensor 156can be any of a variety of sensors which obtain flow rate data. Inselect configurations, the first flow sensor 126 and the second flowsensor 156 can measure different blood properties: such as but notlimited to temperature, Doppler frequency, electrical impedance, opticalproperties, density, ultrasound velocity, concentration of glucose,oxygen saturation and other blood substances (any physical, electricalor chemical blood properties). In one configuration, the first flowsensor 126 and the second flow sensor 156 are clamp on sensors that areexternal to the respective blood withdrawal line 120 and blood deliveryline 150.

Thus, the first flow sensor 126 and the second flow sensor 156 canmeasure a flow characteristic or parameter to generate flow rate data,from which the flow rate, or in certain configurations flow pulsation,variation, frequency change, oscillation component, or flow frequencycomponents can be determined. Alternatively, there can be an additionalsensor (not shown) in addition to the first flow sensor 126 and thesecond flow sensor 156 to measure select blood characteristics orproperties.

It is also understood the flow sensors 126, 156 can be located outsideof the extracorporeal circuit 100. That is, the flow sensors 126, 156can be remotely located and measure in the extracorporeal circuit 100,the changes produced in the blood from the indicator introduction orvalues related to the indicator introduction which can be transmitted ortransferred by means of diffusion, electro-magnetic or thermal fields orby other means to the respective sensor.

The controller 180 is connected to the flow sensors 126, 156, and can beconnected to the pump 170 as well as the renal replacement therapydevice 130. The term “controller” includes signal processors andcomputers, including programmed desk or laptop computers, or dedicatedcomputers for processors. Such controllers 180 can be readily programmedto perform the recited calculations, or derivations thereof, to providedeterminations of the flow rate and transforms of the flow rate data asset forth herein, and seen for example in FIG. 6 . The controller 180can also perform preliminary signal conditioning such as summing onesignal with another signal or portion of another signal. The controller180 can be a stand-alone device such as a personal computer, a dedicateddevice or embedded in one of the components, such as the pump 170 or therenal replacement therapy device 130. The controller 180 can include orbe operably connected to a memory, as well as an input/output devicesuch as a touch screen or keypad or keyboard as known in the industry.Although the controller 180 is shown as connected to the first andsecond flow sensors 126, 156, the pump 170, and the renal replacementtherapy device 130, it is understood the controller can be connected tothe flow sensors, or the flow sensors and the pump, or any combinationof the flow sensors, the pump, and the renal replacement therapy device.

The present method and apparatus provide for measuring blood flowupstream (Q_(H)) of the renal replacement therapy device 130 (such as adialyzer) and blood flow downstream (Q_(V)) of the renal replacementtherapy device and based on the difference between blood flow into andout of the renal replacement therapy device, assessing fluid removal(ultrafiltration) during the blood treatment session (HD) session,wherein the ultrafiltration can be measured substantially continuouslyduring the session. Specifically, the present disclosure is directed toan issue in current approaches of addressing errors in blood flowmeasurement systems with clamp-on sensors, wherein the errors are muchgreater than the necessary accuracy of measurements for determiningfluid removal by the renal replacement therapy device 130.

Sources of errors by clamp-on flow sensors include, but are not limitedto, factory calibration, inconsistency of tubing that the flow sensorswere calibrated on the factory versus in the field tubing, fluctuationsof temperature between measurements, different characteristics of thearterial and the venous flow sensor across the flow range of the renalreplacement therapy device 130 (and/or the pump 170), in that thedifferences may be larger at higher flows and smaller at lower flows, orvice versa.

The present system is directed to reducing the error in the measurementsof the flow sensors on the arterial and venous blood lines 120, 150 bycalibrating, such as matching, the arterial and venous flow sensors 126,156 from a plurality of flow comparisons in the extracorporeal circuit100 which can accommodate current tubing and current patient conditionsin real time, as well as providing for the periodic calibration, such asequalization, throughout the treatment session. The calibration of theflow sensors 126, 156 encompasses matching the first flow sensor 126 andthe second flow sensor 156 either one to the other or to a common point.It is further contemplated the calibration can encompass an equalizationof the signals from the first flow sensor 126 and the second flow sensor156 for a common flow at the known ultrafiltration, wherein the signalsfrom at least one of the flow sensors are adjusted, such as to be equal.As seen in FIG. 2 , the calibration can encompass matching the first andthe second flow sensors 126, 156 as well as equalizing the first and thesecond flow sensors. As seen in FIG. 4 , an offset between the first andthe second flow sensors is eliminated by the equalization.

In a treatment session, a patient is fluidly connected to theextracorporeal circuit 100. Prior to treatment of the blood, such asultrafiltration, by the renal replacement therapy device 130, a bloodflow is established through the extracorporeal circuit 100. Thus, thetreatment session includes the time the patient is operably connected tothe extracorporeal circuit 100, and the blood is merely flowing throughthe extracorporeal circuit untreated, as well as the time the blood isbeing treated by the renal replacement therapy device 130, such asultrafiltration. The treatment session may be 2 hours, 3 hours, fourhours, or longer, and the session is typically dominated by bloodtreatment time. In one configuration, at step 1, typically during thetreatment session but before starting the blood treatment process by therenal replacement therapy device 130 (such as the ultrafiltrationprocess) when blood is passing through the extracorporeal circuit 100(including passing through the blood input line 120 and the blooddelivery line 150) and the ultrafiltration rate is known, such as zero,the blood flow in the renal replacement therapy device (and henceextracorporeal circuit 100) is changed, such as by the controller 180.In one configuration, the change or range of blood flows through theextracorporeal circuit 100 (including the renal replacement therapydevice 130) is within an expected range of blood flow during thetreatment (or within a given extended percentage, such as +/- 5%, or +/-10% or +/- 20% of the expected range). The measured flow rates (thecorresponding generated signals) by each of the first flow sensor 126and the second flow sensor 156 during the known (or zero)ultrafiltration rate are registered, such as received, by the controller180. The registered signals (measured flow rates) from the respectiveflow sensors can be stored or recorded by the controller 180 and in oneconfiguration plotted against the pump flow to provide a correspondingcurve having a slope. The slopes of the arterial and venous flow sensors126, 156 are then calibrated by matching as shown in FIG. 3 .Alternatively, to obtain the effective known (or zero ultrafiltrationrate), the extracorporeal circuit 100 and/or the renal replacementdevice 130 can include a bypass line 140 for the blood flow to bypassexposure to the semi-permeable membrane. In either configuration, (theknown ultrafiltration rate, such as the zero ultrafiltration rate or thebypass, here collectively taken as known ultrafiltration rate), theactual flow through the first flow sensor in the withdrawal line 120must be the same as the flow through the delivery line 150, Bycalibrating, such as matching, adjusting (using a correction factor), orthrough a lookup table, the first flow sensor 126 and the second flowsensor 156 at common flow rates, deviations between the flow sensors canbe accounted for, thereby improving the accuracy of the respective flowmeasurements through the blood withdrawal (arterial) line 120 and theblood delivery (venous) 130 during a treatment session having a givenultrafiltration rate. That is, at a given common flow typically withinthe expected operating range and at the known ultrafiltration rate, thefirst flow sensor 126 and the second flow sensor 156 will provide anequal measurement of the flow by virtue of their calibration. As setforth herein, the calibration can include the controller 180 processingof the signal received from the flow sensors 126, 156.

By obtaining measured flow rates at a minimum of two different flowrates in the calibration process, the first flow sensor 126 and thesecond flow sensor 156 can be calibrated, such as matched. It isunderstood that a plurality of different flow rates can be impartedthrough the extracorporeal circuit 100 and the corresponding flowmeasurements of the first flow sensor 120 and the second flow sensor 156used to calibrate the sensors to each other. Thus, additional flowmeasurements at the known (such as zero) ultrafiltration rate can beused in the calibration of the sensors such as by providing additionaldata points in the corresponding curves or data points in the lookuptables. As more data is obtained, the controller 180 can employ a curvefitting algorithm, such as an adjusting factor known in the art, toaccommodate the additional data.

Calibrating the first flow sensor 126 and the second flow sensor 156 caninclude matching such as graphing the actual flow rate against themeasured flow rate for each of the sensors at a first and a second flowrate in the extracorporeal circuit 100, at the known (such as zero)ultrafiltration rate. Each of the first flow sensor 126 and the secondflow sensor 156 then has an associated curve (relating the respectivemeasured flow rate to the actual or pump flow rate), and the curves canbe matched for measuring flow rate during ultrafiltration, such as forexample, interpolating from the respective curve or adjusting orchanging the curve of one of the flow sensors to match the curve of theremaining flow sensor.

Alternatively, the calibrating can include adjusting the flow rate datafrom one of the first flow sensor 126 and the second flow sensor 156 ata given flow rate to correspond to, or match, or be equal to, the flowrate data of the remaining one of the first flow sensor and the secondflow sensor.

Further, the calibrating can include mechanically adjusting therespective flow sensor or the associated signal at the given flow rate,so that the resulting measured flow rate of the first flow 126 sensorand second flow sensor 156 are equal. That is, if the respective flowsensor has a mechanical adjustment, calibration or tuning, the flowsensor can be matched to the remaining flow sensor, or the actual flowat the known (such as zero) ultrafiltration.

It is further understood the calibrating can be accomplished by applyinga lookup table for the flow rate data obtained by at least one of thefirst flow sensor 126 and the second flow sensor 156 at the respectiveflow rates during the known ultrafiltration. The lookup table can be anyarray that provides an indexing operation, such as index mapping. Thelookup table includes an array or matrix of data that contains itemsthat are searched. The lookup table can be arranged as key-value pairs,where the keys are the data items being searched (looked up) and thevalues are either the actual data or pointers to where the data arelocated.

In one configuration, the calibration to provide matching of the firstflow sensor 126 and the second flow sensor 156 is done during thetreatment session, prior to any ultrafiltration. However, it isunderstood the matching can be performed after, or even during thetreatment session, where the previously obtained flow rate data from thefirst flow sensor 126 and the second flow sensor 156 is then adjustedcorresponding to the matching of the flow sensors. However, it isanticipated that matching the first flow sensor 126 and the second flowsensor 156 during the treatment session, but prior to the bloodtreatment, provides advantages of reducing data processing as well asproviding real time values for guiding the treatment.

In addition to calibrating, such as matching the first flow sensor 126and the second flow sensor 156 before starting the treatment session, aperiodic calibration of the flow sensors, such as equalization, can beperformed to accommodate potential changes over time during a treatmentsession. The ultrafiltration rate of the renal replacement therapydevice 130 can be periodically set to a known ultrafiltration rate, suchas zero, and for at least one blood flow rate through the extracorporealcircuit 100, wherein the measurements of the first flow sensor 126 andthe second flow sensor 156 are measured and then calibrated by beingequalized. The measurement of the first flow sensor 126 can be adjustedto the measurement of the second flow sensor 156, or the measurement ofthe second flow sensor can be adjusted to the measurement of the firstflow sensor, or the measurement of each of the first flow sensor and thesecond flow sensor can be set to a different equal number.

It is contemplated that at the periodic times during the treatmentsession, the ultrafiltration rate is set to a known rate, such as zero,and at least one common flow rate is exposed to the first flow sensor126 and the second flow sensor 156, wherein the first and the secondflow sensors are calibrating by equalizing. It is understood that aplurality of different common flow rates can be exposed to the firstflow sensor 126 and the second flow sensor 156 during the time of theknown ultrafiltration rate. From this plurality of measurements, thefirst flow sensor 126 and the second flow sensor 156 are calibrated,such as matched or equalized. This periodic interval of known (or zero)ultrafiltration rate can be applied by the controller 180 atpredetermined times, or at predetermined thresholds or triggers, ormanually initiated. Thus, at predetermined periods or intervals within atreatment session, the ultrafiltration rate can be set to a known rate,such as zero, and the resulting flow rate data from the first flowsensor 126 and the second flow sensor 156 is used to identify any offsetbetween the first flow sensor and the second flow sensor, as shown inFIG. 3 , so that the flow sensors are calibrated by being equalized bythe removal of the offset.

A further aspect of the present disclosure relates to the collection ofthe flow rate data. Specifically, with respect to obtaining the flowrate data, the flow rate in the blood withdrawal line 120 and the blooddelivery line 150 is generally pulsatile. Therefore, an instantaneousreading or data representing less than a full pulse cycle (or a fewcycles) while accurate of that moment does not provide the necessaryaverage flow rate. To address the pulsatile component of the flow ratein the blood withdrawal line 120 and the blood delivery line 150, thecollection of the flow rate data is taken over a sufficient time tomitigate errors introduced into the measured flows from the pulsatilecomponent. In one configuration, a collection of flow rate data over aperiod of at least 2 cycles has been found satisfactory. Alternatively,the pulsatile flow can be accommodated by choosing the same flow pointin a respective cycle as the start and the finish period of averaging,as shown in FIG. 5 .

By increasing the accuracy of the blood flow measurement (of the flow inthe input line 120 and the delivery line 150), the contribution from therenal replacement therapy device 130 can be determined withcorresponding accuracy. Specifically, Q_(a)= Q_(v) + Q_(UF)

Where Q_(v) is the flow rate in the blood delivery line 150,

Q_(a) is the flow rate in the blood withdraw line 120, and

Q_(UF) is the flow rate from ultrafiltration of the renal replacementtherapy device 130, that is Q_(UF) is the ultrafiltration rate.

Therefore, Q_(UF) = Qa - Qv. By providing the measurements of Q_(v) andQ_(a) within known or acceptable accuracy parameters, the accuracy ofthe ultrafiltration rate Q_(UF) can be thus known and relied upon.

By knowing the ultrafiltration (rate), the volume, or amount, of fluidremoval can be obtained: UF volume (ml) = Q_(UF) * T, where Q_(UF) isthe flow rate from ultrafiltration of the renal replacement therapydevice 130, that is Q_(UF) is the ultrafiltration rate in ml/min unit,and T is the duration which ultrafiltration was turned on (the timeperiod that UF ≠ 0).

The controller 180 is programmed to calibrate, such as match, the firstflow sensor 126 and the second flow sensor 156 by any of the set forthmechanisms, as well as any equivalent. Further, the controller 180 cancalculate the ultrafiltration rate Q_(UF) from the measured flow ratesin the blood withdraw line 120 and the blood delivery line 150 from therespective first flow sensor 126 and the second flow sensor 156. Fromthe calculated ultrafiltration rate, the volume of fluid removal as setforth above. Referring to FIGS. 8A and 8B, the controller can beconfigured to calibrate the first flow sensor 126 and the second flowsensor 156 by matching and equalizing during a given treatment session.

The controller 180 can be configured to maintain a blood flow throughthe extracorporeal circuit 100 while temporarily stoppingultrafiltration during the treatment session to provide a knownultrafiltration rate, register a flow rate from the first flow sensor126 and the second flow sensor 156 during the time of the knownultrafiltration rate, re-calibrate the first flow sensor and the secondflow sensor corresponding to the registered flow rate from the firstflow sensor and the second flow sensor, initiate ultrafiltration andregister a flow rate from the re-calibrated first flow sensor and thesecond flow sensor, and determine the ultrafiltration rate correspondingto the flow rate from the re-calibrated first flow sensor and the secondflow sensor.

Thus, the present disclosure provides a method of measuringultrafiltration rate and cumulative ultrafiltration, by the renalreplacement therapy device 130 in the extracorporeal circuit 100 havingthe pump 170, the renal replacement therapy device configured to providea first and a second known (such as zero) ultrafiltration rate and atarget ultrafiltration rate, and having the blood input line 120delivering blood to the renal replacement therapy device, the permeablemembrane 132, and the blood output line 150 passing blood from the renalreplacement therapy device, the method including the steps of (a)registering, during a first pump flow rate and the first known (such aszero) ultrafiltration rate, a first difference between a first flow ratein the blood input line measured by the first flow sensor 126 and afirst flow rate in the blood output line measured by the second flowsensor 156; (b) registering, during a second pump flow rate and thesecond known (such as zero) ultrafiltration rate, a second differencebetween a second flow rate in the blood input line measured by the firstflow sensor and a second flow rate in the blood output line measured bythe second flow sensor; (c) calibrating, such as matching, the firstflow sensor and the second flow sensor corresponding to the firstdifference and the second difference; and (d) measuring or deriving thetarget ultrafiltration rate at a target pump flow rate from a third flowmeasurement from the calibrated first flow sensor and second flowsensor. As set forth above, it is contemplated the calibrating caninclude matching the slopes from curves associated with the first andsecond measured flow rates of each of the first and second flow sensors.In addition, the first known ultrafiltration rate and the second knownultrafiltration rate can be equal, and can as well be a zeroultrafiltration rate.

In a specific application, the present disclosure provides a method ofmeasuring ultrafiltration by the renal replacement therapy device 130,the renal replacement therapy device configured to provide a known, suchas a zero ultrafiltration rate and a target ultrafiltration rate, in anextracorporeal circuit 100 having the blood input line 120 deliveringblood to the renal replacement therapy device, the pump 170, thepermeable membrane 132, and the blood output line 150 passing blood fromthe renal replacement therapy device, the method including the steps of(i) calibrating, such as matching, prior to ultrafiltration in atreatment session, the first flow sensor 126 measuring blood flow in theblood input line and the second flow sensor 156 measuring blood flow inthe blood delivery line; (ii) recalibrating, such as equalizing, at aknown or zero ultrafiltration rate during the treatment session, thefirst flow sensor and second flow sensor; and (iii) assessing a targetultrafiltration rate based on flow measurements by the recalibratedfirst flow sensor and the second flow sensor. The disclosure furtherprovides for estimating an amount of fluid removal by ultrafiltrationduring the treatment session corresponding to the assessed targetultrafiltration rate. Additional steps can include averaging the flowmeasurement of the first flow sensor 126 and the second flow sensor 156over a plurality of pulses within the measured flow or taking the flowmeasurements across a common point within a flow pulse, to eliminateflow measurement error causing by fluctuation in pulsations in themeasured flow. It is further contemplated the calibrating, such asequalizing steps can be sufficient to accommodate drift/variance betweenthe flow sensors 126, 156 occurring during the treatment session. It isunderstood the calibrating, such as matching or equalizing, can be doneperiodically throughout the treatment session, wherein the assessing isbased on a difference between calibrated flow measurements from thefirst flow sensor 126 and the second flow sensor 156.

The present disclosure provides a further method of measuring a targetultrafiltration rate by the renal replacement therapy device 130, therenal replacement therapy device configured to provide a known, such aszero ultrafiltration rate and the target ultrafiltration rate, andoperably connected to the blood input line 120 delivering blood to therenal replacement therapy device, the pump 170, the permeable membrane132, and the blood output line 150 passing blood from the renalreplacement therapy device, the method including the steps of (a)calibrating the first flow sensor 126 configured to sense a flow in theblood input line and the second flow sensor 156 configured to sense flowin the blood output line, and (b) deriving/calculating the targetultrafiltration rate based on measured flow rates from the calibratedfirst flow sensor and the second flow sensor, wherein the calibratingincludes at least one of:

-   (i) a first flow rate measured by each of the first flow sensor and    the second flow sensor at a first pump flow rate and a first known    ultrafiltration rate, and (ii) a second flow rate measured by each    of the first flow sensor and the second flow sensor at a second pump    flow rate and a second known ultrafiltration rate; and (b)    identifying slopes of curves of the measured first flow rate and    second flow rate against flow standards (or the pump flow) for each    of the first flow sensor and the second flow sensor and matching the    slopes;-   (ii) periodically during the treatment session equalizing, the first    flow sensor and the second flow sensor at a known ultrafiltration    rate;-   (iii) periodically during the treatment session equalizing the first    flow sensor and the second flow sensor, wherein the equalizing is    derived from an offset identified between the first flow sensor and    the second flow sensor at a given pump flow rate and a known    ultrafiltration rate, and adding or subtracting the offset from a    subsequent flow measurement of one of the first flow sensor and the    second flow sensors; and-   (iv) averaging flow measurement of the first flow sensor and second    flow sensor over a sufficient period to encompass at least one    pulsatile cycle within the flow or measuring common start and finish    point of a pulsatile cycle within the flow.

An additional disclosed method includes measuring an ultrafiltrationrate by a renal replacement therapy device 130 in a system having apump, the renal replacement therapy device configured to provide aknown, such as zero, ultrafiltration rate and a target ultrafiltrationrate and having a blood input line delivering blood to the renalreplacement therapy device, a permeable membrane, and a blood outputline passing blood from the renal replacement therapy device, the methodincluding the steps of (a) obtaining, during a first pump flow rate andthe known ultrafiltration rate, (i) a measured first flow rate in theblood input line and (ii) a measured first flow rate in the blood outputline; (b) obtaining, during a second pump flow rate and the targetultrafiltration rate, (i) a measured second flow rate in the blood inputline and (ii) a measured second flow rate in the blood output line; and(c) calculating an ultrafiltration rate corresponding to at least themeasured first flow rate in the blood input line, the measured firstflow rate in the blood output line, the measured second flow rate in theblood input line, and the measured second flow rate in the blood outputline. The method can include the additional step of initiallycalibrating, such as matching, at the known ultrafiltration rate (i) themeasured first flow rate in the blood input line and the measured firstflow rate in the blood output line, and (ii) the measured second flowrate in the blood input line and the measured second flow rate in theblood output line.

Also provided is an alternative method of measuring an ultrafiltrationrate by the renal replacement therapy device 130, the renal replacementtherapy device connected to the pump 170 and configured to provide aknown (such as zero) ultrafiltration rate and a target ultrafiltrationrate and having the blood input line 120 delivering blood to the renalreplacement therapy device, the permeable membrane 132, and the bloodoutput line 150 passing blood from the renal replacement therapy device,wherein the method includes the steps of (a) equalizing, the first flowsensor 126 configured to measure a flow in the blood input line and thesecond flow sensor 156 configured to measure a flow in the blood outputline; (b) operating the replacement therapy device 130 at the targetultrafiltration rate and obtaining a first treatment flow measurementfrom the first flow sensor and a second treatment flow measurement fromthe second flow sensor; and (c) deriving a value of the targetultrafiltration rate based on at least one of the equalized first flowsensor and second flow sensor, the first treatment flow measurement andthe second treatment flow measurement.

Depending upon the calibration used, the present disclosure provides anapparatus for measuring an ultrafiltration rate of the renal replacementtherapy device 130 in an extracorporeal circuit 100 having the pump 170,the renal replacement therapy device configured to establish a first anda second known ultrafiltration rate and a target ultrafiltration rate,the renal replacement therapy device having the blood input line 120delivering blood to the renal replacement therapy device, the permeablemembrane 132, the blood output line 150 passing blood from the renalreplacement therapy device, wherein the apparatus includes (a) the firstflow sensor 126 configured to obtain a blood input line flow rate datain the blood input line; (b) the second flow sensor 156 configured tomeasure a blood output line flow rate data in the blood output line; and(c) the controller 180 connected to the first flow sensor and the secondflow sensor, the controller configured to (i) register, at a first pumpflow rate and the first known ultrafiltration rate, a first differencebetween a first flow rate measured by the first flow sensor and a firstflow rate measured by the second flow sensor and (ii) register, at asecond pump rate and the second known ultrafiltration rate, a seconddifference between a second flow rate measured by the first flow sensorand a second flow rate measured by the second flow sensor, and (iii)identify the target ultrafiltration rate corresponding to the firstdifference and the second difference. It is contemplated the second flowrate and first flow rate may be the same. Similarly, it is contemplatedthe first known ultrafiltration rate and the second knownultrafiltration rate can be equal, including a value of zero.

Thus, the present disclosure provides apparatus for measuring anultrafiltration rate of the renal replacement therapy device 130 in theextracorporeal circuit 100 having the pump 170, the renal replacementtherapy device configured to establish a first known ultrafiltrationrate, a second known ultrafiltration rate, and a target ultrafiltrationrate, the renal replacement therapy device having the blood input line120 delivering blood to the renal replacement therapy device, thepermeable membrane 132, the blood output, or delivery, line 150 passingblood from the renal replacement therapy device, the apparatus includingthe first flow sensor 126 configured to measure a flow rate in the bloodinput line, the second flow sensor 156 configured to measure a flow ratein the blood output line; and the controller 180 connected to the firstflow sensor and the second flow sensor, the controller configured to (i)register a first flow rate measured by the first flow sensor and a firstflow rate measured by the second flow sensor each at a first pump rateand the first known ultrafiltration rate, (ii) register a second flowrate measured by the first flow sensor and a second flow rate measuredby the second flow sensor each at a second pump rate and the secondknown ultrafiltration rate, (iii) calibrate at least one of the firstflow sensor and the second flow sensor corresponding to the first flowrate measured by the first flow sensor, the first flow rate measured bythe second flow sensor, the second flow rate measured by the first flowsensor, and the second flow rate measured by the second flow sensor, and(iv) identify the target ultrafiltration rate from a third flow ratemeasured by the first flow sensor and a third flow rate measured by thesecond flow sensor during the target ultrafiltration rate.

It is contemplated the controller 180 is configured to calibrate thefirst flow sensor and the second flow sensor with a lookup table.Further, the controller 180 can be configured to calculate (i) a firstcurve corresponding to the first flow rate and the second flow ratemeasured by the first flow sensor and (ii) a second curve correspondingto the first flow rate and the second flow rate measured by the secondflow sensor. The controller 180 can be configured to match the firstcurve and the second curve, wherein the matching includes adjusting oneof the first curve and the second curve to a remaining one of the firstcurve and the second curve or fitting one of the first curve and thesecond curve to a remaining one of the first curve and the second curve.The controller 180 can be further configured to quantify the targetultrafiltration rate. As set forth above, the extracorporeal circuit 100can include the bypass line 140 selectively bypassing the renalreplacement therapy device 130. The controller 180 can be configured toregister the first flow rate measured by the first flow sensor 126 andthe first flow rate measured by the second flow sensor 156 each at thefirst pump rate and the first and second known ultrafiltration rate overa sufficient period of data collection for the flow measurement toinclude at least one full cycle of pulsatile flow signal. It is alsounderstood the controller 180 can be configured to register the firstflow rate measured by the first flow sensor 126 and the first flow ratemeasured by the second flow sensor 156 each at a first pump rate and thefirst known ultrafiltration rate at a common point within a pulsatilecycle. The controller 180 can be configured to average the first flowrate measured by the first flow sensor 126 and the first flow ratemeasured by the second flow sensor 156 each at a first pump rate and therespective known ultrafiltration rate over a sufficient period ofregistered flow to include at least one full cycle of pulsatile flowsignal within the average. Also, the controller 180 can be configured toemploy the first known ultrafiltration rate and/or the second knownultrafiltration rate as equal rates, including a zero ultrafiltrationrate.

The present disclosure provides a method of measuring a targetultrafiltration rate by the renal replacement therapy device 130 in theextracorporeal circuit 100 having the pump 170, the renal replacementtherapy device configured to provide a first and a second knownultrafiltration rate and the target ultrafiltration rate, and having theblood input line 120 delivering blood to the renal replacement therapydevice, the permeable membrane 132, and the blood output line 150passing blood from the renal replacement therapy device, the methodincluding (a) measuring, at a first pump flow rate and the first knownultrafiltration rate, (i) a first flow rate in the blood input line bythe first flow sensor 126 and (ii) a first flow rate in the blood outputline by the second flow sensor 156; (b) measuring, at a second pump flowrate and the second known ultrafiltration rate, (i) a second flow ratein the blood input line by the first flow sensor and (ii) a second flowrate in the blood output line by the second flow sensor; (c) matching atleast one of the first flow sensor and the second flow sensorcorresponding to the first flow rate in the blood input line measured bythe first flow sensor, the first flow rate in the blood output linemeasured by the second flow sensor, the second flow rate in the bloodinput line measured by the first flow: sensor, and the second flow ratein the blood output line measured by the second flow sensor; (d)measuring, during the target ultrafiltration rate and a target pump flowrate, (i) a third blood flow rate in the blood input line by the matchedfirst flow sensor and (ii) a third blood flow rate in the blood outputline flow by the matched second flow sensor; and (e) identifying thetarget ultrafiltration rate corresponding to the third blood flow ratein the blood input line measured by the matched first flow sensor andthe third blood flow rate in the blood output line flow measured by thecalibrated second flow sensor. The method can further include, afterstep (e), (f) establishing a known ultrafiltration rate and a givenblood flow rate through the blood input line and the blood output line;(g) identifying an offset between a first measurement of the given bloodflow rate in the blood input line 120 by the first flow sensor 126 and asecond measurement of the given blood flow rate in the blood output line150 by the second flow sensor 156; and (h) adjusting, by the offset, asubsequent flow measurement of at least one of the first flow sensor andthe second flow sensor. That is, the method can further includeequalizing, at least one of the first flow sensor and the second flowsensor corresponding to the flow measured by the first flow sensor andsecond flow sensor during a known ultrafiltration rate and a target pumpflow rate. It is understood the target pump rate can be one of the firstpump rate and the second pump rate. In addition, calibrating the firstflow sensor and the second flow sensor includes adjusting at least oneof the first flow sensor and the second flow sensor. In the method,matching the first flow sensor and the second flow sensor can includeapplying a lookup table. In the method, identifying the targetultrafiltration rate can include quantifying the target ultrafiltrationrate. Further, the known ultrafiltration rate can be a zeroultrafiltration rate and can be obtained by turning off theultrafiltration in the renal replacement therapy device 130 or bypassingthe renal replacement therapy device. In the method a controller can beconfigured to average over a sufficient period of registered flow toinclude at least one full cycle of pulsatile flow signal within theaveraging to reduce, or eliminate, flow measurement error from thefluctuation in pulsations.

While the description is set forth as a renal replacement device 130,the present disclosure encompasses any device for “blood treatment” suchas but not limited to any blood processing including but not limited todialysis, which in turn includes toxin clearance such as by diffusive aswell as conductive therapy including but not limited to hemofiltration,hemodialysis, hemodiafiltration, or Continuous Renal Replacement Therapy(CRRT). The renal replacement therapy device includes a blood treatmentdevice such as any device for imparting the blood treatment. Thus, inone configuration, the blood treatment device, such as the dialyzer, canbe configured to provide controllable transfer of solutes and wateracross a semi permeable membrane separating flowing blood and dialysatestreams. Such a transfer process may include diffusion (dialysis) andconvection (ultra-filtration). The blood treatment device may provideany of a host of other blood treatments, such as chemical treatment,electromagnetic treatment as well as thermal treatment. Though thepresent disclosure is set forth in terms of dialysis in extracorporealrenal replacement therapy renal replacement therapy device, it isunderstood this includes hemodialysis, hemofiltration, andhemodiafiltration.

This disclosure has been described in detail with particular referenceto an embodiment, but it will be understood that variations andmodifications can be effected within the spirit and scope of thedisclosure. The presently disclosed embodiments are therefore consideredin all respects to be illustrative and not restrictive. The scope of theinvention is indicated by the appended claims, and all changes that comewithin the meaning and range of equivalents thereof are intended to beembraced therein.

1. An apparatus for measuring an ultrafiltration rate of a renalreplacement therapy device in an extracorporeal circuit having a pump,the renal replacement therapy device configured to establish a firstknown ultrafiltration rate, a second known ultrafiltration rate and atarget ultrafiltration rate, the renal replacement therapy device havinga blood input line delivering blood to the renal replacement therapydevice, a permeable membrane, a blood output line passing blood from therenal replacement therapy device, the apparatus comprising: (a) a firstflow sensor configured to measure a flow rate in the blood input line;(b) a second flow sensor configured to measure a flow rate in the bloodoutput line; and (c) a controller connected to the first flow sensor andthe second flow sensor, the controller configured to (i) register afirst flow rate measured by the first flow sensor and a first flow ratemeasured by the second flow sensor each at a first pump rate and thefirst known ultrafiltration rate, (ii) register a second flow ratemeasured by the first flow sensor and a second flow rate measured by thesecond flow sensor each at a second pump rate and the second knownultrafiltration rate, (iii) calibrate at least one of the first flowsensor and the second flow sensor corresponding to the first flow ratemeasured by the first flow sensor, the first flow rate measured by thesecond flow sensor, the second flow rate measured by the first flowsensor, and the second flow rate measured by the second flow sensor, and(iv) identify the target ultrafiltration rate from a third flow ratemeasured by the first flow sensor and a third flow rate measured by thesecond flow sensor during the target ultrafiltration rate.
 2. Theapparatus of claim 1, wherein the controller is further configured toperiodically establish a given known ultrafiltration rate and register afourth flow rate measured by the first flow sensor and a fourth flowrate measured by the second flow sensor, and identify a subsequentmeasure of the target ultrafiltration rate at least partly correspondingto the fourth flow rate measured by the first flow sensor and the fourthflow rate measured by the second flow sensor.
 3. The apparatus of claim2, wherein the controller is further configured to register the fourthflow rate measured by the first flow sensor and the fourth flow ratemeasured by the second flow sensor over a sufficient period of datacollection for each measured flow to include at least one full cycle ofa pulsatile flow signal of the measured flow.
 4. The apparatus of claim1, wherein the controller is configured to register the first flow ratemeasured by the first flow sensor and the first flow rate measured bythe second flow sensor over a sufficient period of data collection forthe flow measurement to include at least one full cycle of pulsatileflow signal.
 5. The apparatus of claim 1, wherein the controller isconfigured to employ the respective known ultrafiltration rate as a zeroultrafiltration rate.
 6. The apparatus of claim 1, wherein thecontroller is configured to average the first flow rate measured by thefirst flow sensor and the first flow rate measured by the second flowsensor each at a first pump rate and the known ultrafiltration rate oversufficient period of registered flow to include at least one full cycleof pulsatile flow signal within the average.
 7. An apparatus formeasuring an ultrafiltration rate of a renal replacement therapy devicein an extracorporeal circuit having a pump, the renal replacementtherapy device configured to establish a known ultrafiltration rate anda target ultrafiltration rate, the renal replacement therapy devicehaving a blood input line delivering blood to the renal replacementtherapy device, a permeable membrane, a blood output line passing bloodfrom the renal replacement therapy device, the apparatus comprising: (a)a first flow sensor configured to measure a flow rate in the blood inputline; (b) a second flow sensor configured to measure a flow rate in theblood output line; and (c) a controller connected to the first flowsensor, the second flow sensor, and the renal replacement therapydevice, the controller configured to (i) temporarily impart a knownultrafiltration rate during a treatment session, (ii) identify an offsetbetween the first and the second flow sensor; and (iii) adjust asubsequent flow measurement of at least one of the first flow sensor andthe second flow sensors by the offset.
 8. The apparatus of claim 7,wherein the controller is configured to periodically provide the knownultrafiltration rate as a zero ultrafiltration rate.
 9. The apparatus ofclaim 7, wherein temporarily imparting the known ultrafiltration rate isbetween 1 second and 360 seconds.
 10. The apparatus of claim 7, whereinthe controller is configured to (i) register a first flow rate measuredby the first flow sensor and a first flow rate measured by the secondflow sensor each at a first pump rate and a first known ultrafiltrationrate, (ii) register a second flow rate measured by the first flow sensorand a second flow rate measured by the second flow sensor each at asecond pump rate and a second known ultrafiltration rate, (iii)calibrate at least one of the first flow sensor and the second flowsensor corresponding to the first flow rate measured by the first flowsensor, the first flow rate measured by the second flow sensor, thesecond flow rate measured by the first flow sensor, and the second flowrate measured by the second flow sensor, and (iv) identify the targetultrafiltration rate from a third flow rate measured by the first flowsensor and a third flow rate measured by the second flow sensor duringthe target ultrafiltration rate.
 11. The apparatus of claim 7, whereinthe controller is configured to average the first flow rate measured bythe first flow sensor and the first flow rate measured by the secondflow sensor each at a first pump rate and the known ultrafiltration rateover sufficient period of registered flow to include at least one fullcycle of pulsatile flow signal within the average.
 12. A method ofmeasuring a target ultrafiltration rate by a renal replacement therapydevice in an extracorporeal circuit having a pump, the renal replacementtherapy device configured to provide a first known ultrafiltration rate,a second known ultrafiltration rate, and the target ultrafiltrationrate, and having a blood input line delivering blood to the renalreplacement therapy device, a permeable membrane, and a blood outputline passing blood from the renal replacement therapy device, the methodcomprising: (a) calibrating a first flow sensor configured to sense aflow rate in the blood input line and a second flow sensor configured tosense a flow rate in the blood output line, wherein the calibratingcorresponds to at least (i) a first flow rate in the extracorporealcircuit measured by each of the first flow sensor and the second flowsensor at a first pump flow rate and the first known ultrafiltrationrate, and (ii) a second flow rate in the extracorporeal circuit measuredby each of the first flow sensor and the second flow sensor at a secondpump flow rate and the second known ultrafiltration rate; and (b)identifying the target ultrafiltration rate corresponding to a thirdflow rate measured by the calibrated first flow sensor and the secondflow sensor at a given pump flow rate and the target ultrafiltrationrate.
 13. The method of claim 12, further comprising (i) periodicallyestablishing, during the treatment session, a second knownultrafiltration rate and a given flow rate through the blood input lineand the blood output line and (ii) identifying an offset between ameasured flow rate by the first flow sensor and the second flow sensorduring the known ultrafiltration rate and the given flow rate.
 14. Themethod of claim 13, wherein establishing the second knownultrafiltration rate has a duration between 1 second and 360 seconds.15. The method of claim 12, wherein the first flow rate in theextracorporeal circuit measured by each of the first flow sensor and thesecond flow sensor at a first pump flow rate and the first knownultrafiltration rate includes averaging the first measurement of thegiven blood flow rate in the blood input line by the first flow sensorand the second measurement of the given blood flow rate in the bloodoutput line over a sufficient period of registered flow to include atleast one full cycle of pulsatile flow signal within the average. 16.The method of claim 12, wherein the known ultrafiltration rate is a zeroultrafiltration rate.
 17. A method of operating a renal replacementtherapy device in an extracorporeal circuit having a pump, the renalreplacement therapy device configured to provide a known ultrafiltrationrate and the target ultrafiltration rate, and having a blood input linedelivering blood to the renal replacement therapy device, a permeablemembrane, and a blood output line passing blood from the renalreplacement therapy device, the method comprising: (a) establishing theknown ultrafiltration rate and a given blood flow rate through the bloodinput line and the blood output line; (b) identifying an offset betweena first measurement of the given blood flow rate in the blood input lineby a first flow sensor and a second measurement of the given blood flowrate in the blood output line; and (c) adjusting, by the offset, asubsequent flow measurement of at least one of the first flow sensor andthe second flow sensor.
 18. The method of claim 17, further comprising(a) matching a first flow sensor configured to sense a flow rate in theblood input line and a second flow sensor configured to sense a flowrate in the blood output line, wherein the matching corresponds to atleast (i) a first flow rate in the extracorporeal circuit measured byeach of the first flow sensor and the second flow sensor at a first pumpflow rate and a first known ultrafiltration rate, and (ii) a second flowrate in the extracorporeal circuit measured by each of the first flowsensor and the second flow sensor at a second pump flow rate and asecond known ultrafiltration rate.
 19. The method of claim 17, furthercomprising averaging the first measurement of the given blood flow ratein the blood input line by the first flow sensor and the secondmeasurement of the given blood flow rate in the blood output line oversufficient period of registered flow to include at least one full cycleof pulsatile flow signal within the average.
 20. The method of claim 17,wherein the known ultrafiltration rate is a zero ultrafiltration rate.21. The method of claim 17, wherein establishing the knownultrafiltration rate has a duration between 1 second and 360 seconds.